Lysophospholipid profiles of apolipoprotein E-deficient mice reveal potential lipid biomarkers associated with atherosclerosis progression using validated UPLC-QTRAP-MS/MS-based lipidomics approach

溶血酶- 脂类学 化学 高效液相色谱法 载脂蛋白E 色谱法 内科学 生物化学 医学 疾病 探测器 电气工程 工程类 闪烁体
作者
Yingfei Yan,Zhifeng Du,Chang Chen,Jiaxin Li,Xiang Xiong,Shouxin Zhang,Hongliang Jiang
出处
期刊:Journal of Pharmaceutical and Biomedical Analysis [Elsevier BV]
卷期号:171: 148-157 被引量:10
标识
DOI:10.1016/j.jpba.2019.03.062
摘要

Lysophospholipids (Lyso-PLs) are lipid-derived signaling molecules which were demonstrated to have a strong correlation with the progression of atherosclerosis. In this study, we investigated the influence of high-fat diet on Lyso-PL profiles of atherosclerosis-prone apolipoprotein E-deficient (ApoE−/−) mice and wild type C57BL/6 J mice to find out the potential biomarkers associated with atherosclerosis. Firstly, the quantitative profiling method for Lyso-PLs based on ultra-performance liquid chromatography-quadrupole linear ion trap mass spectrometry (UPLC-QTRAP-MS/MS) was established and validated. Secondly, this method was utilized to quantify 169 targeted Lyso-PLs in plasma samples of ApoE−/− mice and wild type C57BL/6 J mice collected at different time points. Finally, 12 of 37 differential Lyso-PLs were identified as more reliable biomarkers by integrating static metabolomics and time-dependent analyses, among which Lyso-PC/15:0, 18:1/Lyso-PI, 22:5/Lyso-PI and 22:4/Lyso-PI were highly correlated with TCand LDL-C levels. Meanwhile, we found that the Lyso-PL profiles of ApoE−/− mice and C57BL/6 J mice were distinguished by altered metabolism of different Lyso-PLs classes, while C57BL/6 J mice fed with high-fat diet and normal diet were discriminated by the content differences of Lyso-PLs with same fatty acid composition. In conclusion, these results provided detailed changes of Lyso-PL profiles associated with atherosclerosis and the differential Lyso-PLs with reasonable change trends may serve as promising biomarkers for atherosclerosis progression.
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